A novel prognostic score (HAMP) for head and neck cancer patients with single and multiple SBRT-treated lung metastases derived from retrospective analyses of survival outcome.

BACKGROUND: We report on the characterization and introduction of a novel prognostic score for patients undergoing stereotactic body radiotherapy (SBRT) for the treatment of single and multiple pulmonary metastases (PMs) derived from head and neck cancer (HNC). METHODS: In this retrospective study, we examined selected factors associated with progression-free survival (PFS) and overall survival (OS) among 59 patients with HNC treated with SBRT for a total of 118 PMs, between 2009 and 2023. Factors related to survival were included in the prognostic scoring system. RESULTS: Prognostic factors including histology, age, number of metastases, and performance status at first SBRT were weighted differently depending on the strength of correlation to PFS and OS. Total prognostic scores (HAMP) ranged from 13 to 24 points, with a cut-off total score of ≤18 scoring points for patients in a high-risk (HR) subcohort, and of ≥19 scoring points for patients in a low-risk group (LR). Median PFS (23.8 vs. 5.5 months, p < 0.001) and OS (61.3 vs. 16.4 months, p < 0.001) were significantly longer in the low-risk group compared to the high-risk group. CONCLUSION: The HAMP score might be a convenient tool to facilitate individualized treatment decisions and appropriate follow-up. The accuracy and reliability of the score requires further evaluation in prospective studies.

The Neck-Persistency-Net: a three-dimensional, convolution, deep neural network aids in distinguishing vital from non-vital persistent cervical lymph nodes in advanced head and neck squamous cell carcinoma after primary concurrent radiochemotherapy.

PURPOSE: To evaluate the diagnostic performance (DP) of the high-resolution contrast computed tomography (HR-contrast-CT) based Neck-Persistency-Net in distinguishing vital from non-vital persistent cervical lymph nodes (pcLNs) in patients with advanced head and neck squamous cell carcinoma (HNSCC) following primary concurrent chemoradiotherapy (CRT) with [18F]-fluorodeoxyglucose positron emission tomography and high-resolution contrast-enhanced computed tomography ([18F]FDG-PET-CT). Furthermore, the Neck-Persistency-Net's potential to justify omitting post-CRT neck dissection (ND) without risking treatment delays or preventing unnecessary surgery was explored. METHODS: All HNSCC patients undergoing primary CRT followed by post-CRT-ND for pcLNs recorded in the institutional HNSCC registry were analyzed. The Neck-Persistency-Net DP was explored for three scenarios: balanced performance (BalPerf), optimized sensitivity (OptSens), and optimized specificity (OptSpec). Histopathology of post-CRT-ND served as a reference. RESULTS: Among 68 included patients, 11 were female and 32 had vital pcLNs. The Neck-Persistency-Net demonstrated good DP with an area under the curve of 0.82. For BalPerf, both sensitivity and specificity were 78%; for OptSens (90%), specificity was 62%; for OptSpec (95%), sensitivity was 54%. Limiting post-CRT-ND to negative results would have delayed treatment in 27%, 40%, and 7% for BalPerf, OptSens and OptSpec, respectively, versus 23% for [18F]FDG-PET-CT. Conversely, restricting post-CRT-ND to positive results would have prevented unnecessary post-CRT-ND in 78%, 60%, and 95% for BalPerf, OptSens and OptSpec, respectively, versus 55% for [18F]FDG-PET-CT. CONCLUSION: The DP of the Neck-Persistency-Net was comparable to [18F]-FDG-PET-CT. Depending on the chosen decision boundary, the potential to justify the omission of post-CRT-ND without risking treatment delays in false negative findings or reliably prevent unnecessary surgery in false positive findings outperforms the [18F]-FDG-PET-CT.

Prognosis versus Actual Outcomes in Stereotactic Radiosurgery of Brain Metastases: Reliability of Common Prognostic Parameters and Indices.

This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

Survival, Treatment Outcome, and Safety of Multiple and Repeated Courses of Stereotactic Body Radiotherapy for Pulmonary Oligometastases of Head and Neck Squamous Cell Carcinoma.

Current literature regarding survival and treatment outcome of SBRT in patients with pulmonary oligometastatic head and neck squamous cell carcinoma (HNSCC) is limited. Additionally, most of the published studies include metastatic lesions deriving also from primaries with histologies other than SCC when investigating the outcome of SBRT. The aim of the present retrospective study is to explore local control (LC) of treated metastases, progression-free survival (PFS), and overall survival (OS) of exclusively pulmonary oligometastatic HNSCC-patients treated with SBRT. Between 2006 and 2021, a total of 46 patients were treated with SBRT for a maximum of four pulmonary oligometastases (PM) concurrently (mean PM per patient = 2.0; range 1 to 6 PM, total of 92). Of these, 17 patients (37.0%) developed new pulmonary metastases after their first SBRT. Repeated courses of SBRT were required once in 15 patients (88.2%) and twice in 2 patients (11.8%). Median follow-up was 17 months (range, 0-109 months). One year after completion of SBRT, LC rate, PFS, and OS were 98.7%, 37.9%, and 79.5%, respectively. After two years, LC rate, PFS, and OS were 98.7%, 28.7%, and 54.9%; as well as 98.7%, 16.7%, and 31.0% after five years. Radiochemotherapy (HR 2.72, p < 0.001) or radiotherapy as primary treatment (HR 8.60; p = 0.003), as well as reduced patient performance status (HR 48.30, p = 0.002), were associated with lower PFS. Inferior OS correlated with poor performance status (HR 198.51, p < 0.001) and surgery followed by radiochemotherapy (HR 4.18, p = 0.032) as primary treatment, as well as radiotherapy alone (HR 7.11, p = 0.020). Treatment of more than one PM is an independent predictor of impaired OS (HR 3.30, p = 0.016). SBRT of HNSCC-derived PMs results in excellent LC rates and encouraging OS rates of 54.9% at two years along with good tolerability (no more than grade 2 toxicities). Favourable outcome and low toxicity also apply to repeated courses of SBRT of newly emerging PMs.

Dynamic intrafractional position monitoring with implanted fiducial markers for enhanced accuracy in radiotherapy of prostate cancer.

INTRODUCTION: Recent advances in the radiation therapy of prostate cancer have brought a shift toward moderate- and ultra-hypofractionated treatment schedules. Reducing safety margins can broaden the therapeutic window in stereotactic treatments and alleviate concerns for toxicity in high dose-per-fraction treatment schedules. Management of intrafractional motion is a necessity for stereotactic body radiation therapy (SBRT). It can be achieved by performing intrafractional image guidance and position corrections. We evaluate the suitability of such a novel prostate motion management system and its potential benefit for treatment accuracy. METHODS: Intrafractional IGRT was performed for 22 patients during 149 treatment sessions using repeated orthogonal kV-XR imaging of implanted fiducial markers with the ExacTrac Dynamic (EXTD) system. Position measurements were taken four times during each arc of the applied volumetric modulated arc therapy (VMAT). Position correction was performed if translational deviation exceeded 2 mm in any direction. RESULTS: Of 677 single EXTD measurements, 20.6% exceeded the predefined threshold of 2 mm 3D deviation. Without intrafractional corrections, 39.4% of all individual measurements would exceed the threshold. The 3D accuracy could thus significantly be improved, reducing mean 3D shifts from 1.97 (± 1.44) mm to 1.39 (± 1.01) mm by performing intrafractional IGRT. In total, 34% of all treatment sessions required correction of intrafractional position shifts. CONCLUSION: Monitoring of prostate motion using repeated intrafractional orthogonal kV-X-ray-based position measurements of implanted fiducial markers proved to be a reliable method to improve precision of stereotactic irradiations of the prostate. It can prevent unacceptable translation deviations in one third of all sessions.

Current Applications of Artificial Intelligence to Classify Cervical Lymph Nodes in Patients with Head and Neck Squamous Cell Carcinoma-A Systematic Review.

Locally-advanced head and neck squamous cell carcinoma (HNSCC) is mainly defined by the presence of pathologic cervical lymph nodes (LNs) with or without extracapsular spread (ECS). Current radiologic criteria to classify LNs as non-pathologic, pathologic, or pathologic with ECS are primarily shape-based. However, significantly more quantitative information is contained within imaging modalities. This quantitative information could be exploited for classification of LNs in patients with locally-advanced HNSCC by means of artificial intelligence (AI). Currently, various reviews exploring the role of AI in HNSCC are available. However, reviews specifically addressing the current role of AI to classify LN in HNSCC-patients are sparse. The present work systematically reviews original articles that specifically explore the role of AI to classify LNs in locally-advanced HNSCC applying Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and the Study Quality Assessment Tool of National Institute of Health (NIH). Between 2001 and 2022, out of 69 studies a total of 13 retrospective, mainly monocentric, studies were identified. The majority of the studies included patients with oropharyngeal and oral cavity (9 and 7 of 13 studies, respectively) HNSCC. Histopathologic findings were defined as reference in 9 of 13 studies. Machine learning was applied in 13 studies, 9 of them applying deep learning. The mean number of included patients was 75 (SD ± 72; range 10-258) and of LNs was 340 (SD ± 268; range 21-791). The mean diagnostic accuracy for the training sets was 86% (SD ± 14%; range: 43-99%) and for testing sets 86% (SD ± 5%; range 76-92%). Consequently, all of the identified studies concluded AI to be a potentially promising diagnostic support tool for LN-classification in HNSCC. However, adequately powered, prospective, and randomized control trials are urgently required to further assess AI's role in LN-classification in locally-advanced HNSCC.

Frequency and Consequences of Cervical Lymph Node Overstaging in Head and Neck Carcinoma.

Clinical lymph node staging in head and neck carcinoma (HNC) is fraught with uncertainties. Established clinical algorithms are available for the problem of occult cervical metastases. Much less is known about clinical lymph node overstaging. We identified HNC patients clinically classified as lymph node positive (cN+), in whom surgical neck dissection (ND) specimens were histopathologically negative (pN0) and in addition the subgroup, in whom an originally planned postoperative radiotherapy (PORT) was omitted. We compared these patients with surgically treated patients with clinically and histopathologically negative neck (cN0/pN0), who had received selective ND. Using a fuzzy matching algorithm, we identified patients with closely similar patient and disease characteristics, who had received primary definitive radiotherapy (RT) with or without systemic therapy (RT ± ST). Of the 980 patients with HNC, 292 received a ND as part of primary treatment. In 128/292 patients with cN0 neck, ND was elective, and in 164 patients with clinically positive neck (cN+), ND was therapeutic. In 43/164 cN+ patients, ND was histopathologically negative (cN+/pN-). In 24 of these, initially planned PORT was omitted. Overall, survival did not differ from the cN0/pN0 and primary RT ± ST control groups. However, more RT ± ST patients had functional problems with nutrition (p = 0.002). Based on these data, it can be estimated that lymph node overstaging is 26% (95% CI: 20% to 34%). In 15% (95% CI: 10% to 21%) of surgically treated cN+ HNC patients, treatment can be de-escalated without the affection of survival.

Enhanced expression of the sphingosine-1-phosphate-receptor-3 causes acute myelogenous leukemia in mice.

Acute myeloid leukemia (AML) carries a 10-100 fold lower mutational burden than other neoplastic entities. Mechanistic explanations for why a low number of mutations suffice to induce leukemogenesis are therefore required. Here we demonstrate that transgenic overexpression of the wild type sphingosine-1-phosphate receptor 3 (S1P3) in murine hematopoietic stem cells is sufficient to induce a transplantable myeloid leukemia. In contrast, S1P3 expression in more mature compartments does not cause malignant transformation. Treatment with the sphingosine phosphate receptor modulator Fingolimod, which prevents receptor signaling, normalized peripheral blood cell counts and reduced spleen sizes in S1P3 expressing mice. Gene expression analyses in AML patients revealed elevated S1P3 expression specifically in two molecular subclasses. Our data suggest a previously unrecognized contribution of wild type S1P3 signaling to leukemogenesis that warrants the exploration of S1P3 antagonists in preclinical AML models.